Heat Shock Protein Family A Member 1A Attenuates Apoptosis and Oxidative Stress via ERK/JNK Pathway in Hyperplastic Prostate

Abstract

Benign prostatic hyperplasia (BPH) is a prevalent disorder in aging males. It is investigated whether heat shock protein family A member 1A (HSPA1A), a cytoprotective chaperone induced under stress, has been implicated in the development of BPH. RNA-sequencing and single-cell sequencing analyses revealed significant upregulation of HSPA1A in BPH compared to controls. In vitro experiments elucidated that HSPA1A was localized in prostatic epithelium and stroma, with upregulated expression in BPH tissues. Moreover, HSPA1A silencing augmented apoptosis and reactive oxygen species (ROS) accumulation, inhibiting proliferation via ERK/JNK activation, while overexpression reversed these effects in prostatic BPH-1 and WPMY-1 cells. Additionally, ERK1/2 suppression with U0126 rescued the effects of HSPA1A silencing. In vivo, testosterone-induced BPH (T-BPH) rat models treated with the HSPA1A antagonist KNK437 exhibited prostatic atrophy and molecular changes consistent with reduced HSPA1A activity. Finally, we conducted a tissue microarray (TMA) analysis of 139 BPH specimens from Zhongnan Hospital of Wuhan University, which revealed a positive correlation between HSPA1A expression and clinical parameters, including prostate volume (PV), tPSA, fPSA, and IPSS. In conclusion, our findings suggested that HSPA1A attenuated apoptosis and oxidative stress through the ERK/JNK signaling pathway, contributing to BPH pathogenesis.

Keywords

apoptosis / benign prostatic hyperplasia / heat shock protein family A member 1A / oxidative stress / prostate-specific antigen

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